Seven and a half years after a spinal cord injury that cost him all motor and sensory function below his shoulders, Christopher Reeve has recovered sensory function over approximately 70% of his body and 20% of normal motor function. The first return of motor function came in 2000, after five years of a patterned-activity exercise program, and has accelerated with more intensive therapy. The result does not let the former Superman star leap tall buildings, but it has catapulted him and his medical team to the forefront of those challenging the old paradigm for how much recovery is possible for the adult central nervous system.

Mr. Reeve’s case was reported in the September issue of the Journal of Neurosurgery: Spine. It is the first documented occurrence of a patient improving by two American Spinal Injury Association (ASIA) grades of function more than two years after a spinal cord injury when no initial recovery had occurred. “The most important point about this case is that it shows that some recovery is possible even for the worst-case scenario, ASIA grade A patients, who are the majority of spinal cord injury cases,” said lead author John W. McDonald III, MD, PhD. “We believe that long-term dedication to his rehabilitation program was largely responsible. We hypothesize that patterned neuronal activity is one factor that is important after injury in order to optimize spontaneous regeneration,” he elaborated. “This is based on the proven role of neural activity in the normal development of the nervous system, where the same processes are occurring that we are asking to take place after the injury. Less severely injured patients [ASIA grade B or C] might have even better outcomes.” Dr. McDonald is Medical Director of the Spinal Cord Injury Program at Washington University School of Medicine in St. Louis.

POWER POINT PROGRAM

Mr. Reeve’s therapy program includes bicycling with functional electrical stimulation (FES) of the hamstring, quadriceps, and gluteal muscles. It also involves daily range-of-motion physical therapy; surface electrical stimulation to activate the paraspinal, abdominal, wrist extensor, wrist flexor, deltoid, biceps, and triceps muscles; pamidronate to maintain bone mass; and breathing exercises. The program at first included weekly treadmill walking with body-weight support, but that was replaced by weekly aquatherapy once motor recovery began.

Although the case report suggests that functional improvements developed after Mr. Reeve began working with the Washington University clinic in 1999, Mr. Reeve told NEUROLOGY REVIEWS that much of his exercise regimen actually started years earlier. He began using an FES bike and electrostimulation under the direction of specialists at the Kessler Institute for Rehabilitation in West Orange, New Jersey, soon after his injury in 1995. He also credits Kessler’s Erica Druin, RPT, with harnessing his “aggressiveness and competitiveness” by introducing biofeedback monitoring of his shoulder movements. “Thanks to beginning electrostimulation early, I have been able to maintain my muscle mass. My leg and arm measurements today are only about an inch less than they were in 1995, before my riding accident,” Mr. Reeve said.

In 1998, Mr. Reeve added treadmill walking in a weight-supporting harness under the direction of V. Reggie Edgerton, MD, and colleagues at the University of California, Los Angeles (UCLA). The UCLA group theorized that paraplegics with incomplete spinal cord injury who still had upper body control might regain the ability to walk by retraining the spinal cord through repetitive exposure to the afferent and intraspinal activation patterns associated with standing and stepping. Patients are suspended in a body-weight support harness over a treadmill and walk with manual assistance. As the spinal cord “relearns” standing and stepping, support is gradually withdrawn. Over 500 paraplegic patients have regained the ability to walk on level ground, assisted only by a cane, after a 60-day program of treadmill training, but it had not been used with high-spinal injury patients such as Mr. Reeve. The Burke Rehabilitation Center in White Plains, New York, sent two physical therapists to be trained at the UCLA program, and Mr. Reeve continued his treadmill work there on a weekly basis in 1999 until he accidentally subluxated his left hip. Dr. McDonald replaced the treadmill with weekly aquatherapy.

Drs. Daniel Martin and Paul W. Davenport from the University of Florida at Gainesville developed Mr. Reeve’s breathing exercise program. They theorized that reducing the amount of air delivered by ventilator during physical activity might trigger autonomic breathing due to a significant increase in carbon dioxide. Mr. Reeve also uses exercises to strengthen his diaphragm and enable him to breathe without recruiting accessory muscles. He is still dependent on a ventilator but is now able to breathe correctly and unassisted for up to 90 minutes. “A ventilator failure in 1995 would have been terrifying. Now with exercise and training I am able to move my diaphragm and breathe quite well off the vent, which is one of the most comforting aspects of my recovery. My goal for the next year is to get off the vent entirely, which will mean I no longer need care from others 24/7,” he said.

REACHING TOWARD RECOVERY

By early 1998, the benefits of all this effort were apparent in the reduction in complications of his spinal cord injury. These included infections, skin breakdown, heterotopic ossification, autonomic dysreflexia, pathologic bone fractures from osteoporosis, deep venous thrombosis, and acute respiratory distress due to mucous plugging. Yearly infections dropped from 23 in 1996 to eight in 1999, and total days of antibiotic treatment dropped from 169 to 99. During 2001 Mr. Reeve had only three infections, requiring just 18 days of antibiotic treatment. Severe osteoporosis, which had resulted in two pathologic fractures, was also completely corrected by 2002.

“Medication to prevent bone loss, physical activity, or FES alone can limit or stabilize—but not reverse—osteoporosis. The combination can,” Dr. McDonald noted. “In the hundreds of patients we have studied so far with patterned neural activity programs such as the FES bike, the improvement in physical factors such as osteoporosis, reduced risk of infection, maintaining skin integrity, and decreased spasticity is enormous, even in the absence of functional recovery,” he added. “There are huge dollar amounts associated with these changes, and our hope is that this case will help the insurance industry realize that there will be major cost savings from paying for ongoing activity-based therapy for spinal cord injury patients because these programs keep patients out of the hospital. Today, most spinal cord injury patients lose access to the equipment and staff required once they leave an inpatient rehabilitation program, and the duration of inpatient rehabilitation has gotten shorter and shorter over the past 10 years.”

THE “N OF ONE” STUDY

The first sign that something beyond physical benefits was possible for Mr. Reeve appeared in September of 2000, when he suddenly found that he could move his left index finger on command. This was quite unexpected, since he had sustained a classic “hangman’s fracture” of the neck (a Type II odontoid fracture with fracture of the occipital condyle and displacement of the occiput anterior to C-1) in a horseback riding accident on May 27, 1995.

Five years later, magnetic resonance imaging (MRI) showed a central cyst at C-2 and only a rim of white matter (less than 25%) intact. Dr. McDonald pointed out that one positive aspect of this case is that the cystic area is confined to the C-2 level, perhaps because the cervical canal is wider at C-2 and offers more protection for the spinal cord there than at other levels. The limitation of Mr. Reeve’s spinal cord damage was perhaps also due in part to University of Virginia Hospital neurosurgeon John A. Jane, Sr, MD, PhD, who paid meticulous attention to maintaining alignment when turning Mr. Reeve from supine to prone during the postaccident occiput–C-2 fusion.

In November of 2000, Mr. Reeve encountered Dr. McDonald at a neuroscience meeting and showed him the finger movement. A subsequent MRI showed that both tongue movement and finger movement were being coordinated by the correct part of the motor cortex. Dr. McDonald suspected that the patterned neural activity provided by Mr. Reeve’s exercise program might be promoting regeneration and functional reactivation in his central nervous system. He and Mr. Reeve agreed to collaborate on an “N of One” study for the next two years to see what more might be possible.

“I made this project my mission for 2001 and 2002,” Mr. Reeve said. “I had been exercising for maintenance, but I started to exercise for recovery. Under John’s direction I ramped up my exercise to daily three- to four-hour sessions, plus the weekly aquatherapy.” Mr. Reeve traveled back to St. Louis for regular examinations by Dr. McDonald’s team.

By July of 2001, Dr. McDonald had documented an improvement in light touch sensation to 52% of normal, and motor function had improved enough for Mr. Reeve to be reclassified as ASIA grade C. Motor recovery appeared first in the left fingers, then the right hand, then the legs. Mr. Reeve can now move most of the muscles in his upper arms and has some movement in his legs but is unable to stand because his leg muscles are not yet able to oppose gravity. Current sensory function is spared to the S4-5 sacral region. The recovery of 50% of normal pinprick sensation and 66% of normal light touch means that Mr. Reeve can differentiate between hot and cold, has tactile appreciation, and knows when he needs to change his position to avoid skin ischemia. He can sit for up to 16 hours and is able to resume his work.

Dr. McDonald thinks some of this improvement occurred because the FES bike provides patterned neural activity that replaces some of the signals lost below the level of a spinal cord injury. “Neural activity is probably required to optimize spontaneous regeneration as it is for development of the normal central nervous system,” he said.

“N OF ?”

Like most spinal cord injuries, Mr. Reeve’s injury left some spinal cord intact. About 25% of the cord had survived at the injury level, but some of this might be scar tissue, which cannot be differentiated from functional tissue on MRI. “Most spinal cord injury patients, even those ASIA grade A, do have some remaining intact cord,” said Dr. McDonald. “Complete severing of the spinal cord is rare unless the injury is caused by a gunshot or knife attack. The substantial motor and sensory recovery that occurred in this case suggests that small stepwise treatments may produce large gains in function. This heightens the need for new and better ways to detect persistent connections across the lesion in individuals with ASIA grade A injuries.”

The main barrier to wider use of patterned neural activity to promote recovery from spinal cord injury appears to be financial. “We are limited mainly by the availability of FES bikes,” Dr. McDonald admitted. “The bikes currently cost $14,000 to $16,000 each; most insurance will not pay for them, and they are too bulky for easy home use. Also, individuals with spinal cord injury who have successfully integrated back into life do not have time to go to a center three times a week. What is needed for long-term care of spinal cord injury patients is an in-home therapy program they can do in a cost- and time-effective manner,” he said.

While laboratory studies are being conducted to understand the underlying factors in any potential regenerative responses, Dr. McDonald concluded that “the physical benefits alone are sufficient reason to participate in such activity-based therapy programs.”

Mr. Reeve added that one of his hopes is that “this study will also benefit others because insurance companies will get the message that they can save money by providing this type of therapy.”

NR

—Janis Kelly

Suggested Reading
McDonald JW, Becker D, Sadowsky CL, et al. Late recovery following spinal cord injury: case report and review of the literature. J Neurosurg (Spine 2). 2002;97:252-265.

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